Functional contribution of mesencephalic locomotor region nuclei to locomotor recovery after spinal cord injury

Spinal cord injury (SCI) results in a disruption of information between the brain and the spinal circuit. Electrical stimulation of the mesencephalic locomotor region (MLR) can promote locomotor recovery in acute and chronic SCI rodent models. Although clinical trials are currently under way, there is still debate about the organization of this supraspinal center and which anatomic correlate of the MLR should be targeted to promote recovery. Combining kinematics, electromyographic recordings, anatomic analysis, and mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus contribute to locomotor recovery by enhancing motor efficacy in hindlimb muscles, and by increasing locomotor rhythm and speed on a treadmill, over ground, and during swimming in chronic SCI mice. In contrast, glutamatergic neurons of the pedunculopontine nucleus slow down locomotion. Therefore, our study identifies the cuneiform nucleus and its glutamatergic neurons as a therapeutical target to improve locomotor recovery in patients living with SCI.